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Friday, May 8, 2009
Northwest Hall (Chicago Hilton)
12:00 PM
Background:
Autism is a disorder determined by multiple interacting genetic and environmental factors in which immune responses and neuroinflammation appear to influence pathogenic mechanisms and persistence of neurological and behavioral abnormalities.
Objectives:
To identify biomarkers of systemic inflammation in patients with regressive (AUT-R) and non-regressive (AUT-NR) forms of autism.
Methods:
A case-control study of clinical and immunological factors associated with autism was carried out at the intramural autism program of the National Institute of Mental Health. Autism was diagnosed using the ADI-R and ADOS as well as clinical judgment. Regression history was also assessed using the Regression Validation Interview. Regression was defined as language loss and/or loss of social engagement. Serum and plasma samples were obtained from 46 patients with autism (25 AUT-R and 23 AUT-NR; mean age 4.14 years ±1.31) and age-matched typically developing controls (mean age 3.32 ± 1.28). Multiplexed flow cytometric bead assays were used to determine the profile of 27 cytokines, chemokines and growth factors in serum. The Mann-Whitney U-test was used to compare group differences in analyte concentrations. Statistical significance was determined at 0.05.
Results:
CD40 ligand (CD40L), also called CD154 or TNFSF5, was significantly elevated in cases of autism compared to controls (p 0.018). CD40L is a transmembrane glycoprotein related to tumor necrosis factor and is a strong inducer of Th1 cell responses and central to the maintenance and development of B and T cell responses, The chemokine eotaxin (CCL11) and the hematopoietic growth factor, Granulocyte-Macrophage colony stimulating factor (GM-CSF), were identified to be significantly decreased in the serum of patients with autism as compared with controls (p=0.017 and 0.004 respectively). Although the levels of expression of IL-10 and IL-5 were similar in the overall analysis of autism compared to typical control groups, these two cytokines did show significant decreases in the AUT-R patients as compared with typical controls (p 0.019 and 0.048).
Discussion
The elevated concentration of CD40L in serum of patients with autism supports the view that an underlying systemic inflammatory process occurs in patients with this disorder, a condition that may influence overall health, CNS function and behavior. CD40L increases in the serum of patients with autism may result from systemic inflammatory events that exists as co-morbid conditions or from an increase in oxidative stress pathology . CD40L may work as an amplifier of pro-inflammatory and immune responses in the CNS and be involved in processes of neuroglial activation. Reductions in subsets of cytokines such as IL-10, IL-5 and GM-CSF and chemokines such eotaxin, suggests that dysfunction in immune responses occurs in patients with autism.
Conclusions:
Autism is a disorder determined by multiple interacting genetic and environmental factors in which immune responses and neuroinflammation appear to influence pathogenic mechanisms and persistence of neurological and behavioral abnormalities.
Objectives:
To identify biomarkers of systemic inflammation in patients with regressive (AUT-R) and non-regressive (AUT-NR) forms of autism.
Methods:
A case-control study of clinical and immunological factors associated with autism was carried out at the intramural autism program of the National Institute of Mental Health. Autism was diagnosed using the ADI-R and ADOS as well as clinical judgment. Regression history was also assessed using the Regression Validation Interview. Regression was defined as language loss and/or loss of social engagement. Serum and plasma samples were obtained from 46 patients with autism (25 AUT-R and 23 AUT-NR; mean age 4.14 years ±1.31) and age-matched typically developing controls (mean age 3.32 ± 1.28). Multiplexed flow cytometric bead assays were used to determine the profile of 27 cytokines, chemokines and growth factors in serum. The Mann-Whitney U-test was used to compare group differences in analyte concentrations. Statistical significance was determined at 0.05.
Results:
CD40 ligand (CD40L), also called CD154 or TNFSF5, was significantly elevated in cases of autism compared to controls (p 0.018). CD40L is a transmembrane glycoprotein related to tumor necrosis factor and is a strong inducer of Th1 cell responses and central to the maintenance and development of B and T cell responses, The chemokine eotaxin (CCL11) and the hematopoietic growth factor, Granulocyte-Macrophage colony stimulating factor (GM-CSF), were identified to be significantly decreased in the serum of patients with autism as compared with controls (p=0.017 and 0.004 respectively). Although the levels of expression of IL-10 and IL-5 were similar in the overall analysis of autism compared to typical control groups, these two cytokines did show significant decreases in the AUT-R patients as compared with typical controls (p 0.019 and 0.048).
Discussion
The elevated concentration of CD40L in serum of patients with autism supports the view that an underlying systemic inflammatory process occurs in patients with this disorder, a condition that may influence overall health, CNS function and behavior. CD40L increases in the serum of patients with autism may result from systemic inflammatory events that exists as co-morbid conditions or from an increase in oxidative stress pathology . CD40L may work as an amplifier of pro-inflammatory and immune responses in the CNS and be involved in processes of neuroglial activation. Reductions in subsets of cytokines such as IL-10, IL-5 and GM-CSF and chemokines such eotaxin, suggests that dysfunction in immune responses occurs in patients with autism.
Conclusions:
Evidence of activation of the CD40/CD40L pathway is an indicator of systemic inflammation in patients with autism that may be associated with overall effects on the health, neurological and behavioral status.